1. Field of the Invention
This invention relates to the preparation of aqueous formulations containing monomeric, dimeric and oligomeric water soluble organosilane species having a silicon-bonded quaternary ammonium halide functionality and hydrolyzable alkoxy groups and for their application to human skin wherein the monomeric and oligomeric species react on the skin to provide an insoluble, polymeric antimicrobial treatment which is substantive to the skin, is not removed by rinsing, retains its microbial activity while present on the skin and which moisturizes the skin by its presence.
2. Description of the Prior Art
Organosilanes containing quaternary ammonium halides and hydrolyzable alkoxy groups bonded to silicon have been employed in a wide variety of applications. The hydrolyzable groups enable these compounds to form bonds to substrates that contain hydroxy, alkoxy, oxide and similar reactive moieties. Organosilanes have been used to waterproof masonry and brick surfaces, as paint additives, fabric treatments and for surface modification of substrates that enhance miscibility in organic solvents or enable subsequent operations to be conducted on the substrate such as dyeing or painting.
Organosilane quaternary nitrogen compounds have also been employed effectively in eliminating and reducing bacterial, viral and fungal contamination when applied to a variety of surfaces including metal, glass, plastics, rubber, ceramics and fabrics including cellulose, cotton, acetates and nylon.
For health, safety and economical reasons, it is most desirable to apply such antimicrobial quaternized organosilanes from an aqueous medium, which may contain additives and components the purpose of which is to increase stability, provide scent and color, and improve performance.
The stability of aqueous solutions of organosilanes varies from minutes to hours for simple organosilanes such as methyltrimethoxysilane and to weeks for aminoalkylsilanes such as 3-aminopropyltrimethoxysilane. The instability in water of alkoxyorganosilanes is due to intermolecular condensation of the silanol groups generated through hydrolysis of the alkoxy groups to form siloxanes, which on obtaining a certain molecular weight become insoluble in water and precipitate from solution. It is well known to those skilled in the art that adjustment of the pH with acids or bases or the addition of certain surfactants will increase or decrease the rate of self-condensation.
Commercial quaternary ammonium organosilanes are available as 42% active material in methanol under the trademark Dow Coming 5700 (3-(trimethoxysilyl)propyldimethyloctadecyl ammonium chloride) by Aegis Environmental Management, Inc. of Midland, Mich. and Requat 1977 (3-(trimethoxysilyl)-propyldidecylmethyl ammonium chloride) by Sanitized Inc. of New Preston, Conn. Octadecyldimethyl(3-trimethoxysilylpropyl) ammonium chloride (Cat. No. SIO6620.0) as a 60% active solution in methanol, tetradecyldimethyl(3-trimethoxysilylpropyl) ammonium chloride (Cat. No. SIT7090.0) as a 50% solution in methanol and didecylmethyl(3-trimethoxysilylpropyl) ammonium chloride (Cat. No. SID3392.0) as a 42% solution in methanol are offered by Gelest, Inc. of Tullytown, Pa. They are often applied from solvent solutions such as lower alcohols.
Organosilicon ammonium compounds were first taught by Roth in U.S. Pat. No. 3,560,385. The use of these compounds for antimicrobial purposes is taught in U.S. Pat. No. 3,730,701 to Isquith et al. They teach that neutral to alkaline pH values were more effective in algae control, but no claims for stability of aqueous solutions were made.
Algae inhibition was also taught in U.S. Pat. Nos. 3,794,736 and 3,860,709. The inhibition of algae growth on solid surfaces such as cellulose acetate following treatment with organosilane quaternary ammonium materials was described by Abbott et al. in U.S. Pat. No. 3,817,739. Abbott et al. in U.S. Pat. No. 3,865,728 again describes algicidal reduction on fibrous materials including polyesters as well as cellulose acetate. G. Kinstedt in U.S. Pat. No. 4,005,025 claims organosilane quaternaries as being useful in imparting soil release properties to hard surfaces in detergent applications such as dishwashing liquids and general hard surface cleaners, but makes no claims for antimicrobial activity.
U.S. Pat. No. 4,005,028 to Heckert et al. similarly teaches detergent compositions containing zwitterionic or ampholytic detergents and quaternized organosilanes. Similarly, U.S. Pat. No. 4,005,030 by D. Heckert and D. Watt teach detergent formulations useful as oven cleaners, window cleaners or toiler bowl cleaners. No antimicrobial claims are present in the ""025, ""028 and ""030 Patents.
In U.S. Pat. No. 4,282,366 organosilicon ammonium compounds are used to render paper substrates resistant to growth of microorganisms. Similarly, Klein in U.S. Pat. No. 4,394,378 claims 3-(trimethoxysilyl)propyldidecylmethyl ammonium chloride as effective against bacteria and fungi on siliceous surfaces, wood, metal, leather, rubber, plastic and textiles.
Other applications for these compounds include paint additives and shoe treatments in U.S. Pat. No. 4,393,378, dentifrice additives in U.S. Pat. No. 4,161,518, and in contact lens disinfectant solution in U.S. Pat. No. 4,615,882. Canadian Patent No. 1,217,004 to Hardy teaches these compounds are antimicrobial when added to bleach such as sodium hypochlorite and can be used as hard surface cleaners.
U.S. Pat. No. 4,406,892 describes treatment of cellulosic fabrics to prevent the growth of disease causing organisms. Similarly, Burril et al. in U.S. Pat. No. 4,421,796 teach a method of treating textile fibers with a mixture of quaternized organosilane compositions in an emulsion containing polydimethylsiloxanes to improve removal of oily soil.
In U.S. Pat. No. 4,467,013 3-(trimethoxysilyl)propyldimethyloctadecyl ammonium chloride is taught as being useful in the treatment of surgical gowns, dressings and bandages. Homan in U.S. Pat. No. 4,564,456 utilizes organosilicon quaternary ammonium compounds to treat water and inhibit corrosion and metal deposition. Hair conditioning compositions containing 3-(trimethoxysilyl)propyl-dimethyloctadecyl ammonium chloride, when applied at pH 8-10 causing the hair to swell is taught by Stadnick in U.S. Pat. No. 4,567,039.
Aqueous emulsions formed by the use of certain organofunctional cationic silanes, including quaternary ammonium organosilanes such as 3-(trimethoxysilyl)propyl-dimethyloctadecyl ammonium chloride, are taught by Blehm et al. in U.S. Pat. No. 4,361,273. The disclosed oil-in-water emulsions allow the transfer of water immiscible liquids and silanes to the surface of certain substrates with the avoidance of any subsequent rewetting or resolubilization of the silane or water immiscible liquid and its subsequent loss from the surface. The water immiscible liquid utilized to prevent resolubilizing of the cationic silane away from the substrate may be silicone oils, waxes, hydrocarbons, glycols or aliphatic alcohols. The preparation of these emulsions utilize co-surfactants such as nonionic and cationic surfactants and require a homogenizer using high shear conditions and teach that the quaternized organosilane does not hydrolyze to the silanol while in its emulsion form and thus does not polymerize to an insoluble siloxane. These emulsions require a water immiscible liquid as described above with which the quaternized organosilane associates, and that a sufficient shear force, requiring specialized mixers, is necessary to form the emulsion they teach. Blehm et al. teaches the prepared emulsion is utilized to transfer the unhydrolyzed quaternized organosilane to the surface where it is protected against resolubilization by the water immiscible component.
The use of similar oil-in-water emulsion compositions in treating acne vulgaris and ringworm is taught in U.S. Pat. No. 4,908,355 to Gettings and White. This patent teaches a method of treating skin disorders through topical application to the epidermis of an oil-in-water emulsion in which there is a quaternary ammonium organosilane, specifically 3-(trimethoxysilyl)propyldimethyloctadecyl ammonium chloride and a low viscosity, low molecular weight water immiscible liquid silicone fluid, which causes the quaternized silane to penetrate the follicular orifices. The volatile silicone fluid is for the purpose of driving the silane into sebaceous glands and destroying the staphylococcal group of bacteria that may reside there. The formation of these emulsions are essentially the formulations taught in the foregoing ""273 patent. This patent teaches the quaternized silane can be used neat, in an organic solvent or in aqueous solvent solutions. It further teaches a water immiscible component such as an oil, wax or grease must be present and included in the compositions applied to the skin. It does not teach homogeneous aqueous solutions of the quaternary ammonium organosilane nor demonstrate substantiveness and efficacy on skin. The ability of the silane to be applied directly to the skin from aqueous solutions and the ability for the silane to remain on the skin and continue to be antimicrobially active even after repeated rinsings or washings is not taught.
Glass beads treated with organosilane quaternary compounds are described in U.S. Pat. No. 4,682,992 as being used in air filters where antimicrobial qualities are desired. U.S. Pat. No. 4,781,974 teaches wet towelettes having as organosilicon quaternary ammonium compound substantive to the fibers, but does not teach it being transferred to surfaces or skin. Bryant in U.S. Pat. No. 4,797,420 teaches a formulation containing an alkyl dimethyl benzyl ammonium chloride, a nonionic surfactant and a lower alcohol such as isopropanol in water which is used as a disinfectant formulation.
U.S. Pat. No. 4,847,088 to Blank teaches a quaternary organosilane composition such as 3-(trimethoxysilyl)propyldimethyloctadecyl ammonium chloride when combined with an acid in water will increase the antimicrobial effect. Similar antimicrobial properties are claimed in U.S. Pat. No. 5,013,459 for a method and device to dispense ophthalmic fluids, the porous medium of which has been previously treated with an organosilicon quaternary ammonium material.
U.S. Pat. No. 5,411,585 to Avery et al. teaches further methods for the production of stable hydrolyzable organosilane quaternary ammonium compounds to render surfaces antimicrobial when applied as ingredients in hard surface cleaners.
Stabilized aqueous organosilane solutions, including quaternary ammonium organosilane compounds, with stability of weeks to months, are taught by Elfersy et al. in U.S. Pat. No. 5,954,869. These compositions contain a polyol molecule having at least two hydroxy groups which are separated by no more than three intervening atoms and the organosilane. These compositions may be used to coat a food article, a fluid container or a latex medical article. Sugars are the most common stabilizer taught in this patent.
The prior art and open literature disclose the antimicrobial properties of quaternary ammonium organosilanes against a wide range of pathogens including, but not limited to:
Bacteria:
Gram Positive Bacteria:
Citrobacter freundii 
Citrobacter diversus 
Corynebacterium diptheriae 
Diplococcus pneumoniae 
Micrococcus sp. (I)
Micrococcus sp. (II)
Micrococcus sp. (III)
Mycobacterium spp.
Staphylococcus albus 
Staphylococcus aureus 
Staphylococcus citrens 
Staphylococcus epidermidis 
Streptococcus faecalis 
Streptococcus pyogenes 
Gram Negative Bacteria:
Acinetobacter calcoaceticus 
Enterobacter aerogenes 
Enterobacter aglomerans (I)
Enterobacter aglomerans (II)
Escherichia coli 
Klebsiella pneumoniae 
Nisseria gonorrhoeae 
Proteus mirabilis 
Proteus morganii 
Proteus vulgaris 
Providencia spp.
Pseudomonas
Pseudomonas aeruginosa 
Pseudomonas fragi 
Salmonella choleraesuis 
Salmonella enteritidis 
Salmonella gallinarum 
Salmonella paratyphi A 
Salmonella schottmuelleri 
Salmonella typhimurium 
Salmonella typhosa 
Serratia marcescens 
Shigella flexnerie Type II
Shigella sonnei 
Virbrio cholerae 
Viruses:
Adenovirus Type IV
Feline Pneumonitis 
Herpes Simplex Type I and II
HIV-1 (AIDS)
Influenza A (Japan)
Influenza A2 (Aichi)
Influenza A2 (Hong Kong)
Parinfluenza (Sendai)
Poliovirus
Reovirus
Respiratory Synctia 
Fungi and Mold:
Alternaria alternata 
Asperigillus niger 
Aureobasidium pullulans 
Candida albicans 
Cladosporium cladosporioides 
Drechslera australiensis 
Gliomastix cerealis 
Microsporum audouinii 
Monilia grisea 
Phoma fimeti 
Pithomyces chartarum 
Scolecobasidium humicola 
Trychophyton interdigitale 
Trychophyton mentagrophytes 
The open literature and the prior art cited above do not teach topical application of aqueous solutions of organosilicon quaternary ammonium compounds to the skin, nor do they teach such application methods utilizing these compositions as being broad spectrum antimicrobial methods which remain on the skin, bond to the skin, are substantive to it and resist removal by washing or rinsings.
A number of aqueous hand lotion formulations containing solubilized quaternary ammonium organosilanes, suitable as antimicrobial hand sanitizers, antimicrobial skin cleansers, liquid antimicrobial hand soaps and antimicrobial skin moisturizing lotions have been prepared. The formulations disclosed in this instant invention impart both antimicrobial and moisturizing functionality to the skin. These functional characteristics remain on the skin throughout normal daily activities for up to sixty-four hours. All formulations contain organosilane quaternary ammonium compounds, specifically 3-(trimethoxysilyl)propyloctadecyldimethyl ammonium chloride, 3-(trimethoxysilyl)-propyldidecylmethyl ammonium chloride, the trisilanol derivatives and the polysiloxanol derivatives and mixtures thereof. Other quaternary ammonium organosilicon compounds, the silanol derivatives and mixtures thereof, such as 3-(trimethoxysilyl)-propyldimethyltetradecyl ammonium chloride, 3-(trimethoxysilyl)propyldimethylhexadecyl ammonium chloride, 3-(dimethoxymethylsilyl) propyldimethyloctadecyl ammonium chloride and 3-(methoxydimethylsilyl)propyldimethyloctadecyl ammonium chloride may also be employed, as would be apparent to those skilled in the art.
Prior art has failed to recognize that quaternary ammonium organosilanes containing hydrolyzable groups can form antimicrobially active, clear solutions in aqueous media which are stable over extended periods of time, which do not require addition of immiscible materials to form antimicrobially effective emulsions and also do not require adjustment of pH. The compositions of the present invention can be readily and easily prepared by adding the quaternary ammonium organosilane composition to purified semiconductor grade water. The addition of lower alcohols in up to 80 % concentration to lower the freezing point of the solution, to increase evaporation rates of the aqueous media from the skin, to increase the rate of antimicrobial effects, to enhance cleansing properties, or to increase solubility of other additives, does not affect the extended stability or performance of the solution. The preparative method of the present invention provides stable, clear, quaternary ammonium organosilane solutions. The solutions can be applied to human skin and animal skin to deposit on the treated skin an antimicrobially active quaternary ammonium organosilane derivative which is substantive to the skin, is not removed by subsequent rinsings, which retains its antimicrobial activity against a broad range of pathogens, will remain active on the skin for up to 64 hours and retards moisture loss from the skin.
The present invention provides methods for application of quaternary ammonium organosilane compositions to the skin and the disclosed compositions are readily applied to the skin when incorporated as ingredients in the amounts of 0.01 to 4.0 percent into carrier solutions. Carrier solutions as defined in the present invention are aqueous solutions or alcoholic water solutions. All formulations are homogeneous and may be scented and/or colored and may contain water-soluble additives to enhance performance and viscosity. The active quaternary ammonium organosilane ingredients are applied to the skin as liquid, fluid, gel or solid solutions. When applied to the skin, the quaternary ammonium organosilane species forms a molecular layer adjacent to and on the skin.
Prior art has demonstrated that deposition of organosilicon quaternary ammonium compounds onto substrates from aqueous solutions is achievable. It has also been extensively demonstrated that quaternary organosilicon ammonium compounds are effective against a broad spectrum of pathogens including gram positive and gram-negative bacteria, viruses and fungi, including molds and yeasts. On application to the skin, the organosilicon quaternary ammonium compounds form a water insoluble molecular layer, which is substantive to the skin and will remain through a minimum of nine rinses. Skin treated with the above described materials are resistant to infection from gram positive and gram negative bacteria, viruses, and fungi, including mold and spores. Application of these formulations promotes a smooth feeling to the skin and protects against redness and chapping due to the moisturizing qualities of the material.
Conversely, prior art has not demonstrated that aqueous solutions of the organosilicon quaternary compounds may be effectively applied to the skin where the quaternary ammonium organosilane moiety forms a polymeric network over the skin and is bonded to it, whether covalently, electrostatically or through hydrogen bonding. While on the skin it retains its antimicrobial character and is effective against the range of pathogens described above.
The compositions of the present invention are non-toxic, efficient and economical for use as topical antimicrobial skin-treatments. There are no reports of methods that teach aqueous solutions of quaternary ammonium organosilanes being applied as aqueous formulations to the skin for antimicrobial effect or purpose. The substantiveness, continuing antimicrobial activity and moisturizing qualities are new, novel and unprecedented. Conventional non-silicon containing quaternary ammonium compounds, when applied to the skin are easily removed by rinsing or hand washing. They exhibit no substantive characteristics on skin. Following application, organosilane quaternary ammonium compounds are substantive to the skin and exhibit antimicrobial activity while on the skin, reducing or eliminating existing pathogens and preventing reinfection by reducing or eliminating additional pathogens introduced after application. They do not demonstrate irritability to the skin presumably due to their unique bonding abilities which effectively places a barrier of organosiloxy moieties between the skin surface and the antimicrobial active ammonium cation. This antimicrobial barrier prevents reinfection on subsequent introduction of pathogens and functions as a moisturizing layer by slowing moisture loss from the surface of the skin.
Accordingly, in one embodiment, this invention provides a composition for antimicrobially treating human or animal skin that is comprised of an effective amount of the water soluble quaternary ammonium organosilane and an aqueous carrier.
In another embodiment, this invention provides a method to prepare a clear water-stable composition comprising the quaternary ammonium organosilane of this invention and water or a water and lower alcohol solution.
In a further embodiment, this invention provides a method of antimicrobially treating skin that consists of contacting the skin with an aqueous composition containing quaternary ammonium organosilanes for a period of time to sufficiently render the substrate antimicrobially active.
In addition, the present invention provides a method to treat skin and nails with the quaternary ammonium organosilane having adhered thereto.
In a further embodiment, the present invention provides a composition for a liquid antimicrobial skin cleanser comprising an aqueous solution of quaternary ammonium organosilanes and additives, and thickeners which when applied to the skin will cleanse the skin of dirt and oils and simultaneously deposit an antimicrobial molecular layer of quaternary ammonium organosilanes on the skin surface.
In yet another embodiment of this invention, a method is provided to prepare aqueous compositions containing quaternary ammonium organosilanes incorporating deionized-water with or without various described additives which may be colored or scented without decreasing the stability or antimicrobial character, efficacy or substantiveness when the composition is subsequently applied to the skin.
A further embodiment of the present invention provides a method and compositions for coating skin and nails with a quaternary ammonium organosilane which is antimicrobial, substantive to the skin and which is not removed by rinsing and washing.
In yet another embodiment of the present invention provides a method for treating skin that retards loss of moisture from the skin by its presence and bonded character to the skin and is a moisturizer for the skin.
Thus, the present invention provides a method for rendering skin, nails and hair antimicrobial, with a quaternary ammonium organosilane which adheres to the skin, hair and nails, retains its antimicrobial activity for up to 64 hours and prevents reinfection of the skin, hair and nails on subsequent contact with infection producing pathogens.
It is apparent to those skilled in the art that quaternary ammonium organosilanes may be incorporated into a variety of skin care products without the addition or presence of water immiscible additive oils, greases or waxes to enhance moisturizing qualities and impart substantive antimicrobial properties. These products include all solutions containing quaternary ammonium organosilanes that contact the skin and which do not contain water immiscible organic additives such as oils, waxes or greases.
Additional advantages and benefits of the intention are set forth in the description which follows and it is to be understood that the foregoing general description and the following detailed description are explanatory and are not restrictive of the invention as claimed.